HDLs in apoA-I transgenic Abca1 knockout mice are remodelednormally in plasma but are hypercatabolized by the kidney

• Published in: Journal of lipid research Vol. 46
• Main Authors: Lee, Ji-Young, Timmins, Jenelle M., Mulya, Anny, Smith, ThomasL, Zhu, Yiwen, Rubin, Edward M., Chisholm, Jeffrey W., Colvin, Perry L., Parks, John S.
• Format: Journal Article
• Language: English
• Published: United States 05.07.2005
• Subjects: 60 APPLIED LIFE SCIENCES; apolipoprotein A-I ATP binding cassette transporter A1 highdensity lipoprotein; APOLIPOPROTEINS; BASIC BIOLOGICAL SCIENCES; BLOOD-PLASMA CLEARANCE; CATABOLISM; CELLOBIOSE; DECAY; DISEASES; IN VIVO; KIDNEYS; LIVER; MICE; MUTATIONS; ORGANS; PATIENTS; PLASMA; PROTEINS
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M500179-JLR200

Patients homozygous for Tangier disease have a near absence of plasma HDL as a result of mutations in ABCA1 and hypercatabolize normal HDL particles. To determine the relationship between ABCA1 expression and HDL catabolism, we investigated intravascular remodeling, plasma clearance, and organ-specific uptake of HDL in mice expressing the human apolipoprotein A-I (apoA-I) transgene in the Abca1 knockout background. Small HDL particles (7.5 nm), radiolabeled with 125I-tyramine cellobiose, were injected into recipient mice to quantify plasma turnover and the organ uptake of tracer. Small HDL tracer was remodeled to 8.2 nm diameter particles within 5 min in human apolipoprotein A-I transgenic (hA-ITg) mice (control) and knockout mice. Decay of tracer from plasma was 1.6-fold more rapid in knockout mice (P<0.05) and kidney uptake was twice that of controls, with no difference in liver uptake. We also observed 2-fold greater hepatic expression of ABCA1 protein in hA-ITg mice compared with nontransgenic mice, suggesting that overexpression of human apoA-I stabilized hepatic ABCA1 protein in vivo.